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• Established serology reference laboratories
• Antigen-specific ELISA
• Micro-neutralization assay
• HI
• Used reverse genetic technology to create a vaccine strain based
on H3N2-A/Taiwan/641/2006 virus strain in 45 days.
International collaboration in vaccine R&D
and technology transfer
To ensure we will have a self-sufficient pandemic flu vaccine supply
tomorrow, the flu vaccine self-manufacturing strategic plans
provided financial assistance to the NHRI Vaccine Center, so it has
the most technically competent staff and a cGMP pilot plant facil-
ity to manufacture prototype pandemic flu vaccine during times of
emergency.
Through an R&D grant from the National Science Council and
Department of Health Vaccine Center, NHRI has successfully:
• Collaborated with the Japan NIID for technology transfer, in
particular flu QC tests
• Established a P2+ facility for emergency MDCK cell-based flu
virus vaccine production at 100,000 doses capacity
• Developed bioprocesses to characterize potential virus seeds
with both growth profiles and master seed files
• Implemented a cGMP pilot plant with a scale of 250,000 doses
per three months for pandemic flu vaccine development.
NHRI has also:
• Established a collaboration agreement for international
prototype pandemic flu vaccine clinical trials to be performed in
Taiwan
• Assisted Taiwan vaccine manufacturer(s) to negotiate and obtain
flu vaccine manufacturing technology transfer (cell-culture
based vaccine production)
• Assisted Taiwan institutes in negotiating and obtaining
intellectual properties for reverse genetic technology to generate
pandemic flu mutant strains for vaccine production.
The NHRI Vaccine Center has achieved the following:
• Completed the MDCK master cell bank and RG-14 H5N1 virus
seed validation
• Developed MDCK cell-based processes for emergency
production of H5N1 vaccine candidates
• Completed pre-clinical toxicology studies
• Completed preliminary stability studies on the storage condition
for vaccine bulk and alum-absorbed vaccine candidate
• Made ready more then 10,000 doses (based on 15ug of HA) of
vaccine bulk for emergency use
• Implemented and validated essential QC tests
• Formulated the NHRI H5N1 vaccine candidate in alum, which
could elicit protection against wild type H5N1 challenges in
mouse models.
Industrialization
The Flu Vaccine Self-Manufacturing Task Forces had considered how
to assist Taiwan CDC in drafting a long-term flu vaccine supply
contract as the incentive plan for investors to build a flu vaccine self-
manufacturing plant in Taiwan. The following terms of incentives
have been put forward:
• A ten-year contract to supply four million doses of flu vaccine
• Technical assistance to build a flu vaccine
manufacturing plant with a 16 million dosage
capacity for seasonal flu vaccine
• Provision of flu vaccine marketing analysis and
foreign financial assistance
• Technical assistance for the Taiwan Vaccine
Company to negotiate and obtain intellectual
properties for reverse genetic technology to generate
pandemic flu mutant strains for vaccine production
• Technical assistance for flu vaccine manufacturing
plants to set up cGMP QC lab for product release tests
• Technical assistance for flu vaccine manufacturing
plants to produce clinical lots and initiate IND
submission for phase 1, 2 and 3 trials.
Nobody knows when a pandemic flu will happen, but
everyone knows that there will be a shortage of flu
vaccines in the world. Vaccine stockpiling is one
option that the Taiwan Government has taken. The
question is how many doses we should keep each
season, since flu vaccine have only a one-year expiry
date. If we keep too much it will be very expensive.
Some flu vaccine companies are working on antigen-
sparing using adjuvants. For emergency cases during
pandemic flu in Taiwan, we should have 0.3 to 0.5
million doses of current-year flu vaccines stockpiled.
This is based on the adjuvant vaccines that are
normally 10-50 times better than non-adjuvanted
vaccines. Therefore, 0.3 million could be converted
into three million doses. In this case, Taiwan CDC has
supported those vaccine companies currently conduct-
ing antigen-sparing clinical trials, so we can have
first-hand information on whether this type of vaccine
will work for Taiwan’s people.
During the vaccine development process, one of the
major bottlenecks is the evaluation of IND and clinical
trials approval. To fast-track flu vaccine (pandemic or
normal flu vaccines), the Taiwan Government understands
that this is a good opportunity to financially assist the
Taiwan FDA and Center for Drug Evaluations to build up
infrastructure to enhance vaccine evaluation and licens-
ing processes, in particular the IND and clinical trials
protocols approval. To this end, CDE and Taiwan FDA
have completed flexible policies for pandemic flu vaccine
approval for clinical trials and product registration.
Conclusion
To minimize the risk of vaccine supplies, the Taiwan
government has successfully organized and imple-
mented regional flu vaccine manufacturing plans. The
Taiwan CDC and NHRI Vaccine Center have initiated
and collaborated on a global pandemic flu vaccine
R&D programme. NHRI Vaccine has established a P2+
GMP biological plant for H5N1 flu vaccine emergency
production. The Taiwan Government has initiated a
build/operate/own incentive package for a regional
vaccine self-manufacturing facility with the capabil-
ity of producing 16 million doses of seasonal flu
vaccines.